Enhanced cross-recognition of SARS-CoV-2 Omicron variant by peptide vaccine-induced antibodies

Abstract

Current vaccines against SARS-CoV-2, based on the original Wuhan sequence, induce antibodies with different degrees of cross-recognition of new viral variants of concern. Despite potent responses generated in vaccinated and infected individuals, the Omicron (B.1.1.529) variant causes breakthrough infections, facilitating viral transmission. We previously reported a vaccine based on a cyclic peptide containing the 446-488 S1 sequence (446-488cc) of the SARS-CoV-2 spike (S) protein from Wuhan isolate. To provide the best immunity against Omicron, here we compared Omicron-specific immunity induced by a Wuhan-based 446-488cc peptide, by a Wuhan-based recombinant receptor-binding domain (RBD) vaccine and by a new 446-488cc peptide vaccine based on the Omicron sequence. Antibodies induced by Wuhan peptide 446-488cc in three murine strains not only recognized the Wuhan and Omicron 446-488 peptides similarly, but also Wuhan and Omicron RBD protein variants. By contrast, antibodies induced by the Wuhan recombinant RBD vaccine showed a much poorer cross-reactivity for the Omicron RBD despite similar recognition of Wuhan and Omicron peptide variants. Finally, although the Omicron-based 446-488cc peptide vaccine was poorly immunogenic in mice due to the loss of T cell epitopes, co-immunization with Omicron peptide 446-488cc and exogenous T cell epitopes induced strong cross-reactive antibodies that neutralized Omicron SARS-CoV-2 virus. Since mutations occurring within this sequence do not alter T cell epitopes in humans, these results indicate the robust immunogenicity of 446-488cc-based peptide vaccines that induce antibodies with a high cross-recognition capacity against Omicron, and suggest that this sequence could be included in future vaccines targeting the Omicron variant.

Oral administration of a recombinant modified RBD antigen of SARS-CoV-2 as a possible immunostimulant for the care of COVID-19

“…Furthermore, since the RBD is the outermost region of the virus and mutations can define its interaction with the hACE2 receptor [ 22 , 23 ], our results showed that RBD and RBD-P stimulate the production of IgG in the serum of experimental animals, in which IgGs produced recognize both the Wuhan and Omicron BA.1 RBDs (Additional file 1 : Figure S3). Aparicio et al, [ 78 ] found antibodies induced by Wuhan RBD peptide in mice cross-react with Omicron peptides. Less recognition was observed in sera obtained from males compared to females, although the recognition profile, in general, is like the recognition of the Wuhan RBD and Omicron (Additional file 1 : Figure S3).…”

Mutated trimeric RBD vaccines: a platform against variants of concern

“…Thus, shorter immunogens based on important epitopes, e.g. small proteins like the candidate designed by He at al or peptide vaccines that induce neutralizing antibodies not elicited by the native proteins, 5 would allow activating new B cell clones specific for the variant sequence not imprinted by original antigenic priming, leading to a higher crossreactivity against new variants. The strategy proposed be He et al could be suitable for this approach, by including the adequate sequence according to the predominant variants.…”